Traumatic peripheral nerve injuries are among the most common problems encountered in clinical neurology and neurosurgery, and while microsurgical techniques have improved outcome, functional recovery is often less than would be desired. Recent evidence has shown that soluble substances from denervated peripheral nerve have the ability to promote axon regeneration. This suggests that degenerating nerve or associated tissue such as Schwann cells may release diffusible trophic factors which support and guide axon regrowth. In addition, trophic factors may differ between nerves, allowing anatomical and functional specificity of reinnervation. The proposed study will examined the role of trophic factors in regeneration of motor and sensory axons of the rat sciatic nerve. The first part will characterize the growth promoting effects of denervated nerve on regenerating axons in vivo, including evaluation of individual nerve specificity and differentiation between motor and sensory axons in their response to trophic factors. The second part will be isolation and characterization of the trophic factors from denervated nerve that are responsible for these actions. This will be performed by using biochemical separation techniques in conjunction with in vitro and in vivo assays of neural growth promoting activities. The third part will be an attempt to improve recovery of transfected rat sciatic nerve by the use of crude and purified growth factors as an adjunct to surgical repair. Hopefully, a combined surgical and biochemical approach to nerve injuries will result in improved functional recovery.